Work will be continued on each of the three major parts: (1) in vivo immunosuppression by tumor promoter; (2) effects of tumor-promoter treatment of lymphocytes on immune response of these cells; and (3) cellular and molecular effects of promoter on lymphocytes. The major focus of in vivo work will be to determine the recovery of immune function in animals on long-term promoter treatment. Work on the second part of this project, in vitro immune effects, will focus on studies of suppressor cell activation. Brief TPA treatment activates suppressor function. We will begin to investigate this model by testing whether cell division, protein synthesis, RNA synthesis, or ornithine decarboxylase induction are required to activate suppressor function by using inhibitors of each process. The suppressive factors released by TPA-treated cells will also be investigated. These factor(s) appear to be in the 150K to 200K molecular weight range. The third area of investigation will focus on studies of the differences between antigen-primed fully differentiated lymphocytes and naive cells. Promoter finds both populations but does not induce ODC or increase receptor aggregation in fully differentiated cells while performing both functions in naive cells. We will assess postbinding events such as internalization of receptor and will examine the promoter receptor (recently shown to copurify with protein kinase in a partial purification) to see if some receptor property is altered. In addition, preliminary studies indicating that promoter has no effect on fully differentiated helper and suppressor cell function will be continued.